التفاصيل البيبلوغرافية
| العنوان: |
Phase II trial of the histone deacetylase inhibitor romidepsin in patients with recurrent/metastatic head and neck cancer |
| المؤلفون: |
Haigentz, Missak1,2 mhaigent@montefiore.org, Kim, Mimi3, Sarta, Catherine2, Lin, Juan3, Keresztes, Roger S.4, Culliney, Bruce5, Gaba, Anu G.1, Smith, Richard V.2, Shapiro, Geoffrey I.6,7, Chirieac, Lucian R.8, Mariadason, John M.1, Belbin, Thomas J.9, Greally, John M.10, Wright, John J.11, Haddad, Robert I.6,7 |
| المصدر: |
Oral Oncology. Dec2012, Vol. 48 Issue 12, p1281-1288. 8p. |
| مصطلحات موضوعية: |
*SQUAMOUS cell carcinoma, *CANCER treatment, *HISTONE deacetylase inhibitors, *CLINICAL trials, *HEAD & neck cancer treatment, *CANCER relapse, *METASTASIS |
| مستخلص: |
Summary: Objectives: Patients with advanced squamous cell carcinoma of the head and neck (SCCHN) have limited treatment options. Inhibition of histone deacetylases (HDACs) represents a novel therapeutic approach warranting additional investigation in solid tumors. Methods: A phase II trial of single agent romidepsin, an HDAC inhibitor, was performed in 14 patients with SCCHN who provided consent for pre- and post-therapy samples of accessible tumor, blood and uninvolved oral mucosa. Romidepsin was administered at 13mg/m2 as a 4-h intravenous infusion on days 1, 8 and 15 of 28day cycles, with response assessment by RECIST every 8weeks. Results: Objective responses were not observed, although 2 heavily pretreated patients had brief clinical disease stabilization. Observed toxicities were expected, including frequent severe fatigue. Immunohistochemical analysis of 7 pre- and post-treatment tumor pairs demonstrated induction of p21Waf1/Cip1 characteristic of HDAC inhibition, as well as decreased Ki67 staining. Exploratory microarray analyses of mucosal and tumor samples detected changes in gene expression following romidepsin treatment that were most commonly associated with regulation of transcription, cell cycle control, signal transduction, and electron transport. Treatment with romidepsin did not alter the extent of DNA methylation of candidate gene loci (including CDH1 and hMLH1) in SCCHN tumors. Conclusions: Single agent romidepsin has limited activity for the treatment of SCCHN but can effectively achieve tumor-associated HDAC inhibition. Although tolerability of romidepsin in this setting may be limiting, further evaluation of other HDAC inhibitors in combination with active therapies may be justified. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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